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PDBsum entry 4lsp
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Viral protein/immune system
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PDB id
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4lsp
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Contents |
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347 a.a.
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216 a.a.
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208 a.a.
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References listed in PDB file
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Key reference
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Title
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Multidonor analysis reveals structural elements, Genetic determinants, And maturation pathway for HIV-1 neutralization by vrc01-Class antibodies.
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Authors
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T.Zhou,
J.Zhu,
X.Wu,
S.Moquin,
B.Zhang,
P.Acharya,
I.S.Georgiev,
H.R.Altae-Tran,
G.Y.Chuang,
M.G.Joyce,
Y.D.Kwon,
N.S.Longo,
M.K.Louder,
T.Luongo,
K.Mckee,
C.A.Schramm,
J.Skinner,
Y.Yang,
Z.Yang,
Z.Zhang,
A.Zheng,
M.Bonsignori,
B.F.Haynes,
J.F.Scheid,
M.C.Nussenzweig,
M.Simek,
D.R.Burton,
W.C.Koff,
J.C.Mullikin,
M.Connors,
L.Shapiro,
G.J.Nabel,
J.R.Mascola,
P.D.Kwong.
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Ref.
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Immunity, 2013,
39,
245-258.
[DOI no: ]
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PubMed id
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Abstract
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Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected
donors, and are potential templates for an effective HIV-1 vaccine. However, the
stochastic processes that generate repertoires in each individual of >10(12)
antibodies make elicitation of specific antibodies uncertain. Here we determine
the ontogeny of the VRC01 class by crystallography and next-generation
sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120
cocrystal structures reveal VRC01-class recognition to be remarkably similar. B
cell transcripts indicate that VRC01-class antibodies require few specific
genetic elements, suggesting that naive-B cells with VRC01-class features are
generated regularly by recombination. Virtually all of these fail to mature,
however, with only a few-likely one-ancestor B cell expanding to form a
VRC01-class lineage in each donor. Developmental similarities in multiple donors
thus reveal the generation of VRC01-class antibodies to be reproducible in
principle, thereby providing a framework for attempts to elicit similar
antibodies in the general population.
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